Evaluation by electrocardiographic and inflammatory parameters of β-adrenergic stimulation-induced myocardial damage in mice

Aim: The study deals with following questions: May the β-adrenergic stimulant "isoproterenol" leading to inflammatory/ischemic histopathologic changes in mice myocardium cause electrocardiographic alternations, as well? Additionally, may "isoproterenol" induced myocardial ischemia be prevented by H3 receptor agonist "Imetit"? Methods: Four groups were constructed with balb-c mice: Saline (SF), isoproterenol (ISO), Imetit (IMT), and a combination of IMT+ISO. Pre-condition lasted 7 days, for each days IMT and ISO+IMT groups were pretreated with oral 10 mg/kg Imetit. In both groups of ISO and ISO+IMT, 85 mg/kg isoproterenol was injected subcutaneously on the last two days to induce ischemia. At the end of pre-condition, two ECG leads are obtained (lead-I and "Z") under anesthesia. Hearts were removed for histological evaluation: sections were stained with Hematoxylin-Eosin (H&E), and tissue level of inflammatory parameters IL-1β, TNF-alpha, MCP-1 were evaluated with indirect-immunoperoxidase staining. Results: We found the J-wave area in lead-Z being a new ECG marker for ISO-induced myocardial ischemia. Both QJ interval and QRS duration increased due to ischemia. H&E examination supported ECG findings, MCP-1 increased in ischemic myocardium whereas IL-1β and TNF-α cytokines were unchanged. These alterations were not seen in pretreated animals with Imetit, except MCP-1. Imetit alone increased both PQ interval and QRS duration. Conclusion: The J-wave area in lead-Z seems to be sensitively correlated to the histological finding of ISO-induced myocardial ischemia in mice. We considered that H3 receptor might present on myocardial cells membrane, basing on increased PQ interval and increased QRS duration due to H3R agonist Imetit.